Enhanced Tumor Diagnostic and Therapeutic Effect of Mesoporous Silica Nanoparticle-Mediated Pre-targeted Strategy
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Improving the targeting efficiency of imaging agents or anticancer drugs has become essential in the current primary mission to enhance the diagnostic or therapeutic effects. To improve the tumor diagnosis and therapy effect, a promising drug-delivery and targeting strategy was established based on the bioorthogonal chemistry.
The delivery system was composed of the pre-targeting carrier Biotin-MSNs-DBCO nanoparticles and the azido cargoes. The fluorescence probe 1-(3-azidopropyl) fluorescein (FITC-N3) and ruthenium N-heterocyclic carbene complex N3-S-S-NHC-Ru were synthesized and served as the tumor imaging and therapy probes, respectively. The cell imaging and viability was investigated by the Biotin-MSNs-DBCO pre-targeted for 4 h in colonic carcinoma (HeLa) cells.
For the tumor cell imaging, Biotin-MSNs-DBCO could react with FITC-N3 rapidly and completely in 20 min with 93% yields. The fluorescence intensity of tumor cells was obviously increased by the Biotin-MSNs-DBCO pre-targeted. The cytotoxicity of the ruthenium complex N3-S-S-NHC-Ru was significantly improved appropriately three times with the IC50 (half inhibitory concentration) value of 6.68 ± 1.29 μM and enhancement of the mitochondrial dysfunction.
The pre-targeting nanoparticle Biotin-MSNs-DBCO could selectively capture the azido compounds in tumor cells, which provided a site-specific target for the cargoes and then resulted in an enhancement of diagnostic or therapeutic effects.
Key wordsanticancer bioorthogonal chemistry mesoporous silica nanoparticle pre-targeting ruthenium complex
Enhanced permeability and retention
Electrospray ionization mass
Flourier transform infrared spectra
High performance liquid chromatography
Mitochondrial membrane potential
Mesoporous silica nanoparticles
3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide
2-azidoethyl (2-((2-hydroxyethyl)disulfanyl)ethyl) N-heterocyclic carbene ruthenium complex
N-heterocyclic carbene ruthenium complex
Nuclear magnetic resonance
Strain-promoted alkyne azide cycloaddition
Transmission electron microscopy
ACKNOWLEDGMENTS AND DISCLOSURES
This work was financially supported by National Natural Science Foundation of China (21501074 and 21371082), Natural Science Foundation of Jiangsu Province (BK20151118), the 333 Project of Jiangsu Province (BRA2016518) and the Key Youth Medical Talent Project of Jiangsu Province (QNRC20162016626 and QNRC20162016629).
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